Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma

NCT ID: NCT02902965

Last Updated: 2020-03-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-20
• Study Completion Date: 2018-10-26

Brief Summary

This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma.

Detailed Description

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoeitic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with bortezomib and dexamethasone in subjects with relapsed/relapsed and refractory multiple myeloma.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ibrutinib+ Bortezomib+ Dexamethasone

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Ibrutinib 840 mg orally, once daily continuously starting day 1 of cycle 1 until confirmed disease progression, unacceptable toxicity or other protocol specified reason for discontinuation

Bortezomib

Intervention Type: DRUG

Cycles 1-8: (21-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 4, 8, and 11 of each Cycle Cycles 9-12: (42-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 8, 22 and 29 of each Cycle

Dexamethasone

Intervention Type: DRUG

Cycles 1-8: (21-day cycle): Dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle Cycles 9-12: (42-day cycle): Dexamethasone 20 mg orally on days 1, 2, 8, 9, 22, 23, 29 and 30 of each cycle Cycles 13+ (28-day cycle): Dexamethasone 40 mg orally once weekly

Dose adjustment of dexamethasone to 10 mg on days specified during cycles 1-12 and 20 mg weekly during cycles 13+ is recommended for subjects >75 years of age.

Following implementation of Protocol Amendment 4, dexamethasone administration was reduced to Days 1, 4, 8 and 11 during each 21-day cycle (Cycles 1-8) and on Days 1, 8, 22, 29 on each 42-day cycle (Cycles 9-12) and unchanged thereafter.

Interventions

Ibrutinib

Ibrutinib 840 mg orally, once daily continuously starting day 1 of cycle 1 until confirmed disease progression, unacceptable toxicity or other protocol specified reason for discontinuation

Intervention Type: DRUG

Bortezomib

Cycles 1-8: (21-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 4, 8, and 11 of each Cycle Cycles 9-12: (42-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 8, 22 and 29 of each Cycle

Intervention Type: DRUG

Dexamethasone

Cycles 1-8: (21-day cycle): Dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle Cycles 9-12: (42-day cycle): Dexamethasone 20 mg orally on days 1, 2, 8, 9, 22, 23, 29 and 30 of each cycle Cycles 13+ (28-day cycle): Dexamethasone 40 mg orally once weekly

Dose adjustment of dexamethasone to 10 mg on days specified during cycles 1-12 and 20 mg weekly during cycles 13+ is recommended for subjects >75 years of age.

Following implementation of Protocol Amendment 4, dexamethasone administration was reduced to Days 1, 4, 8 and 11 during each 21-day cycle (Cycles 1-8) and on Days 1, 8, 22, 29 on each 42-day cycle (Cycles 9-12) and unchanged thereafter.

Intervention Type: DRUG

Other Intervention Names

Imbruvica; Velcade

Eligibility Criteria

Exclusion Criteria

• Measurable disease defined by at least one of the following:

• Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM) multiple myeloma SPEP ≥0.5 g/dL)
• Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis
• Adequate hematologic, hepatic and renal function
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

• Subject must not have primary refractory disease
• Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or carfilzomib)
• Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening
• Plasma cell leukemia, primary amyloidosis, or POEMS syndrome
• Unable to swallow capsules or disease significantly affecting gastrointestinal function
• Requires treatment with strong CYP3A inhibitors
• Women who are pregnant or breast feeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: collaborator

Pharmacyclics Switzerland GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bernhard Hauns, MD

Role: STUDY_DIRECTOR

Pharmacyclics Switzerland GmbH

Locations

Fakultní nemocnice Brno

Brno, , Czechia

Fakultní nemocnice Hradec Králové

Nový Hradec Králové, , Czechia

Fakultní nemocnice Ostrava

Ostrava-Poruba, , Czechia

Všeobecná fakultní nemocnice v Praha

Prague, , Czechia

Helios-Kliniken Berlin-Buch

Berlin, , Germany

Vivantes Klinikum Spandau

Berlin, , Germany

Universitätsklinikum Jena

Jena, , Germany

Klinikum der Universität München Campus Grosshadern

München, , Germany

251 General Air Force Hospital

Athens, , Greece

General Hospital of Athens "Alexandra"

Athens, , Greece

General Hospital of Athens "Evangelismos"

Athens, , Greece

General Hospital of Athens "LAIKO"

Athens, , Greece

University General Hospital of Patra

Pátrai, , Greece

General Hospital of Thessaloniki "G. Papanikolau"

Thessaloniki, , Greece

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, , Italy

Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori

Meldola (FC), , Italy

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Ospedale degli Infermi

Rimini, , Italy

Azienda Ospedaliera S. Maria di Terni

Terni, , Italy

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, , Spain

ICO Badalona-Hospital Germans Trias i Pujol

Badalona, , Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario Madrid Sanchinarro

Madrid, , Spain

Clinica Universidad de Navarra

Pamplona, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario Dr. Peset

Valencia, , Spain

Ankara University Medical Faculty

Ankara, , Turkey (Türkiye)

Dokuz Eylul University Medicine Faculty

Izmir, , Turkey (Türkiye)

Erciyes University Medical Faculty

Kayseri, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Countries

Czechia; Germany; Greece; Italy; Spain; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PCYC-1139-CA

Identifier Type: -

Identifier Source: org_study_id